title: Extraocular muscle atrophy and central nervous system involvement in chronic progressive external ophthalmoplegia.
abstract: BACKGROUND
  Chronic progressive external ophthalmoplegia (CPEO) is a classical mitochondrial ocular disorder characterised by bilateral progressive ptosis and ophthalmoplegia. These ocular features can develop either in isolation or in association with other prominent neurological deficits (CPEO+). Molecularly, CPEO can be classified into two distinct genetic subgroups depending on whether patients harbour single, large-scale mitochondrial DNA (mtDNA) deletions or multiple mtDNA deletions secondary to a nuclear mutation disrupting mtDNA replication or repair. The aim of this magnetic resonance imaging (MRI) study was to investigate whether the ophthalmoplegia in CPEO is primarily myopathic in origin or whether there is evidence of contributory supranuclear pathway dysfunction.
  
  
  METHODS
  Ten age-matched normal controls and twenty patients with CPEO were recruited nine patients with single, large-scale mtDNA deletions and eleven patients with multiple mtDNA deletions secondary to mutations in POLG, PEO1, OPA1, and RRM2B. All subjects underwent a standardised brain and orbital MRI protocol, together with proton magnetic resonance spectroscopy in two voxels located within the parietal white matter and the brainstem.
  
  
  RESULTS
  There was evidence of significant extraocular muscle atrophy in patients with single or multiple mtDNA deletions compared with controls. There was no significant difference in metabolite concentrations between the patient and control groups in both the parietal white matter and brainstem voxels. Volumetric brain measurements revealed marked cortical and cerebellar atrophy among patients with CPEO+ phenotypes.
  
  
  CONCLUSIONS
  The results of this study support a primary myopathic aetiology for the progressive limitation of eye movements that develops in CPEO.
authors.affiliation: Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Yu-Wai-Man
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Smith
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Firbank
authors.forename: Grant
authors.initials: G
authors.lastname: Guthrie
authors.forename: Stuart
authors.initials: S
authors.lastname: Guthrie
authors.forename: Grainne S
authors.initials: GS
authors.lastname: Gorman
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Douglass M
authors.initials: DM
authors.lastname: Turnbull
authors.forename: Philip G
authors.initials: PG
authors.lastname: Griffiths
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blamire
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: Patrick
authors.initials: P
authors.lastname: Yu-Wai-Man
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002451:Cell Compartmentation; D002490:Central Nervous System / Q000473:pathology*; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics; D005123:Eye / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D009133:Muscular Atrophy / Q000473:pathology*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics / Q000473:pathology*; D009929:Organ Size; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial